Role of Human Cripto-1 in Tumor Angiogenesis

Abstract

CR-1 appears to have an important role in the multistep process of angiogenesis.

Regulation of Cripto-1 Signaling and Biological Activity by Caveolin-1 in Mammary Epithelial Cells

“…Since c-src and MAPK pathways have been shown to be critical for Cr-1-mediated cell migration and invasion, Cav-1 might normally antagonize Cripto-1 function by impairing its ability to transmit downstream signaling through these intracellular signaling molecules. 24,25 These observations are consistent with previous in vitro and in vivo studies demonstrating that Cav-1 negatively regulates the p42/p44 MAPK and c-src activity by directly binding to the catalytic domains of these kinases through the CSD. 34 Furthermore, mammary gland tissues of Cav-1 null mice show hyperactivation of MAPK and upregulation of cyclin D1, providing a molecular basis for the increased cell proliferation in Cav-1 null mammary epithelial cells.…”

“…24,25 Briefly, EpH4 WT, EpH4 Cr-1, EpH4 Cav-1, and EpH4 Cr-1/Cav-1 cells or FVB/N, Cav-1 ϩ/Ϫ /CR-1, and Cav-1 Ϫ/Ϫ /CR-1 primary cells at passage 2 were seeded in 12-well plates at 2 ϫ 10 5 per well. The Boyden chambers were incubated overnight at 37°C, and the cells that had migrated or invaded the Matrigel through the filter and attached to the bottom of the membrane were stained with a crystal violet solution.…”

“…20 -23 Cripto-1 can also enhance endothelial cell migration and invasion in vitro and stimulate angiogenesis in vivo. 24 In mouse and human mammary epithelial cells and in cervical and breast carcinoma cells, Cripto-1 has been shown to activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3Ј kinase (PI3K)/AKT and the cytoplasmic tyrosine kinase c-src, through binding of CR-1 to the GPI cell surface-linked heparan sulfate proteoglycan glypican-1. [25][26][27] Furthermore, transgenic mouse models have demonstrated that overexpression of a human CR-1 transgene in the mammary gland under the control of the mouse mammary tumor virus (MMTV) or the whey acidic protein promoter results in multifocal mammary hyperplasias and adenocarcinomas in approximately 30 to 50% of multiparous mice.…”

Cripto-1: At the Crossroads of Embryonic Stem Cells and Cancer

“…Cripto-1 can also function as a potent angiogenic protein both in vitro and in vivo, enhancing the proliferation, migration and invasion of human umbilical vascular endothelial cells and stimulating their differentiation into vascular-like structures in matrigel. Likewise, overexpression of Cripto-1 promotes in vivo neovascularization of MCF-7 xenografts, supporting a role for Cripto-1 in modulating tumor angiogenesis (Bianco et al, 2005a). Since HIF-1 can enhance Cripto-1 expression by directly binding to the Cripto-1 promoter, it is possible that the hypoxic microenvironment within the growing tumor might enhance Cripto-1 expression, which in turn induces new vessel formation to sustain tumor growth ).…”

TDGF1 is a novel predictive marker for metachronous metastasis of colorectal cancer

“…TDGF1, also known as CRYPTO, Crypto-1, or CR-1, is expressed in various cancer tissues of different species (8)(9)(10)(11)(12)(13)(14)(15)(16)(20)(21)(22)(23). Previous in vitro and in vivo reports show that TDGF1 regulates signaling pathways and cellular mechanisms as an oncogene (23)(24)(25)(26).…”